Diagnostic accuracy of point-of-care biomarkers for multiple sclerosis relapse in the emergency department: a systematic review

Abstract

Background: Differentiating a true multiple sclerosis (MS) relapse from pseudo-relapse, infection, metabolic disturbance, or another neurological disorder is important in emergency care. An objective blood-based point-of-care biomarker offers a route toward faster relapse assessment, although its diagnostic performance and readiness for emergency-department implementation is uncertain. Objective: This systematic review evaluated the diagnostic performance and clinical applicability of fluid biomarkers for identifying acute MS relapse or related inflammatory disease activity. Methods: PubMed, Scopus, Web of Science Core Collection, and the Cochrane Library/CENTRAL were searched through July 2026. We include original studies evaluating blood or cerebrospinal-fluid biomarkers in relation to clinical relapse, contrast-enhancing lesions, or composite inflammatory disease activity. Diagnostic performance, biomarker platform, reference standard, sampling timing, and emergency-care applicability were synthesized qualitatively according to PRISMA principles. Results: We include ten studies in the final qualitative analysis. Serum neurofilament light chain (sNfL) was the most investigated candidate. Prospective studies reported moderate discrimination for clinical or composite disease activity, while multianalyte proteomic and metabolomic panels produced stronger discrimination in selected cohorts. No included study validated a true bedside assay in an emergency-department population. Considerable heterogeneity existed in reference standards, sampling intervals, thresholds, platforms, and clinical populations. Conclusion: sNfL represents the most mature blood candidate for objective assessment of MS inflammatory activity. Prospective ED-specific validation using rapid platforms and prespecified thresholds remains necessary.